An RCT 1 randomized a total of 2 763 women with coronary disease (CHD), younger than 80 years, and postmenopausal with an intact uterus to either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate or placebo. Follow-up averaged 4.1 years. Overall, there were no significant differences between groups in the primary outcome, myocardial infarction (MI) or CHD death (hormone 172 vs placebo 176; relative hazard, RH 0.99, 95% CI 0.80 to 1.22). The lack of an overall effect occurred despite a net 11% lower low-density lipoprotein cholesterol level and 10% higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group (each P<.001). There was a statistically significant time trend, with more CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5. More women in the hormone group than in the placebo group experienced venous thromboembolic events (RH 2.89, 95% CI 1.50 to 5.58) and gallbladder disease (RH 1.38, 95% CI 1.00 to 1.92). There was no difference in total mortality (hormone 131 vs placebo 123 deaths; RH 1.08, 95% CI 0.84 to 1.38).
Subsequent unblinded follow-up for 2.7 years (HERS II) 2 included 2 321 women (93% of those surviving). There were no significant decreases in rates of primary CHD events or secondary cardiovascular events among women assigned to the hormone group compared with the placebo group in HERS, HERS II, or overall. The unadjusted RH for CHD events in HERS II was 1.00 (95% CI 0.77 to 1.29); and overall (HERS+HERS II) 0.99 (95% CI 0.84 to 1.17). The overall RHs were similar after adjustment for potential confounders and differential use of statins between treatment groups (RH 0.97, 95% CI 0.82 to 1.14), and in analyses restricted to women who were adherent to randomized treatment assignment (RH 0.96, 95% CI 0.77 to 1.19).
Date of latest search:
Primary/Secondary Keywords